Acid zirconium phosphate and alkaline hydrous zirconium oxide materials for sorbent dialysis

ABSTRACT

A combination of acid zirconium phosphate and alkaline hydrous zirconium oxide are utilized as ion-exchange materials, for example, in sorbent dialysis. The combination provides for dialysate regeneration while maintaining constant and controlled levels of Na + , HCO 3   − , and pH.

This application claims the benefit under 35 U.S.C. §119(e) of priorU.S. Provisional Patent Application No. 61/101,280, filed Sep. 30, 2008,which is incorporated in its entirety by reference herein.

FIELD OF THE INVENTION

The present invention relates to ion-exchange materials and inparticular, to acid zirconium phosphate materials and alkaline hydrouszirconium oxide materials that are useful, for example, in sorbentdialysis.

BACKGROUND OF THE INVENTION

Single-pass and sorbent dialysis systems both provide treatment forpatients with acute or chronic kidney disease. Both systems deliverdialysate to the dialyzer in prescribed amounts to cleanse the blood ofimpurities, correct the patient's body chemistry, and remove excessfluid. Sorbent dialysis differs from traditional single-pass dialysis inthat sorbent systems use less water than single-pass machines and do notrequire special plumbing. Single-pass systems use approximately 120liters of water during a typical 4-hour treatment. In single-passdialysis, a water treatment system is required to continuously pumppurified water into the system to be blended with the bicarbonate andacid bath to create the final dialysate. This requires special plumbingto connect the single-pass machine to both the water treatment systemand to a drain into which the used dialysate and rejected source waterare disposed.

By utilizing sorbent technology, a dialysis system can providehighly-pure dialysate for 3- to 8-hour treatments using only 6 liters ofpotable tap water. The sorbent cartridge purifies the initial dialysateand continuously recirculates and regenerates the dialysate throughoutthe treatment. This not only eliminates the need to purchase andmaintain an expensive water treatment system, but provides a high degreeof transportability compared to conventional dialysis systems. Becausesorbent systems do not require special wiring or plumbing, sorbentdialysis can be performed almost anywhere: in dialysis centers, hospitalrooms, nursing homes, and home-care environments.

Sorbent systems provide a gentle way to achieve an electrolyte andchemical balance. Single-pass machines deliver a constant dialysateprescription to the patient. This forces the patient's body chemistry tochange to match the dialysate prescription. This can cause some of thecommon side effects often associated with single-pass dialysis, such asnausea, cramping, and hypotension. During a sorbent dialysis treatment,urea is dismantled within the cartridge and combined with other solutesto replenish the sodium chloride and sodium bicarbonate required tocorrect the patient's body chemistry. Because the patient's body fluidvolume is much larger than the dialysate volume, the patient is able tocontrol the dialysate. The sorbent cartridge performs multiple tasks: itserves as a dialysate purification system, maintains dialysate pHbalance, and binds uremic wastes.

Six liters of potable tap water and prescribed amounts of sodiumchloride, sodium bicarbonate, and dextrose are used to create theinitial dialysate solution. This mixture is then passed through thesorbent cartridge. As it flows through the cartridge, bacteria,pyrogens, endotoxins, metals, and organic solutes are removed from theinitial dialysate. The purified dialysate is stored in the dialysatereservoir bag until it is circulated to the dialyzer. Once it leaves thedialyzer, the spent dialysate and the patient's ultrafiltrate fluid passthrough the sorbent cartridge, where both are converted into partiallyregenerated dialysate, known as cartridge effluent. An infusate systemadds calcium, carbon dioxide, magnesium, and potassium to form a fullyregenerated dialysate, which then flows back into the dialysatereservoir bag, ready to be sent to the dialyzer.

Zirconium phosphate (ZrP) particles and hydrous zirconium oxide (HZO)particles are used as ion-exchange materials and are particularly usefulas a sorbent material in regenerative kidney dialysis. Zirconiumphosphate in the sodium or hydrogen form serves as a cation exchangerand absorbs cations such as ammonium (NH₄ ⁺), calcium (Ca⁺), potassium(K⁺), and magnesium (Mg²⁺). In exchange for absorbing these cations, ZrPreleases two other cations, sodium (Na⁺) and hydrogen (H⁺). Hydrouszirconium oxide in the acetate form acts as an anion exchanger. Thus, itbinds anions such as phosphate (P⁻) and fluoride (F⁻) and releasesacetate (CH₃COO⁻) in exchange. Hydrous zirconium oxide is also anexcellent adsorbent for metals, such as iron, mercury, lead, andaluminum.

The sorbent cartridge containing ZrP and HZO ion-exchange materials hasbeen historically used for the REDY (REgenerative DialYsis) system. TheREDY sorbent cartridge consists of several layers through which useddialysate passes: i) a purification layer consisting of activatedcharcoal; ii) an enzyme layer consisting of urease; iii) a cationexchange layer consisting of ZrP; iv) an anion exchange layer consistingof HZO; and v) an adsorbent layer consisting again of activated carbon.During regenerative dialysis, the used dialysate moves up through thelayers of the cartridge. The enzymatic urease converts urea intoammonium carbonate. The ammonia and ammonium ions are then removed bythe zirconium phosphate in exchange for H⁺ and Na⁺ ions. The carbonatefrom the urea hydrolysis then combines with H⁺ to form bicarbonate (HCO₃⁻) and carbonic acid (H₂CO₃). Carbonic acid is an unstable organic acid;most of it quickly breaks down into water and carbon dioxide molecules(CO₂). The HZO (containing acetate as a counter ion) removes HCO₃ ⁻, P⁻,and other anions (e.g., F⁻ in water), and releases acetate. Theactivated carbon absorbs organic metabolites such as creatine, uricacid, and nitrogenous metabolic waste of the patient as well as chlorineand chloramines from the water. The CO₂ gas bubbles are vented from thecartridge.

The safety and efficacy record of the REDY system has been wellestablished. Nevertheless, the REDY cartridge can produce a variation ofdialysate composition and pH during the treatment with the production ofbicarbonate and carbonic acid, and the continuous release of Na⁺ by thecartridge.

Current zirconium phosphate (ZrP) based dialysis applications, such asthe REDY cartridges, contain a large amount of lattice H⁺ ions even whenit is titrated to a pH range of 5.75-6.45. During sorbent dialysis,these lattice H⁺ ions of ZrP will react with the NaHCO₃ in dialysatecausing initial decomposition of bicarbonate to CO₂ gas and adsorptionof Na⁺. After depletion of H⁺ ions and loading up of Na⁺ in ZrP,progressively, the NH₄ adsorption mechanism will then switch toion-exchange with adsorbed Na⁺ in ZrP. This will cause increasingrelease of Na⁺, accompanied by a rise of HCO₃-level, and formation ofCO₃ ²⁻ from urea hydrolysis. Consequently, the use of ZrP alone forsorbent dialysis can cause a variation in Na⁺, HCO₃ ⁻, and pH inregenerated dialysate during treatment.

The Na⁺ and bicarbonate level in the dialysate can also vary dependingon the blood urea nitrogen (BUN) level of the patient. Thus, the REDYdialysis therapy has to provide several dialysate prescriptions tobalance the pH and the Na⁺ level in the patient for the correction ofhyper and hyponatremia. Also a conductivity alarm system is generallypresent to keep the Na⁺ level in the dialysate below a safe limit.

A need exists for ion-exchange materials for sorbent dialysis systemsthat can maintain steady and predictable dialysate compositions. Sorbentcartridges containing such materials could regenerate spent dialysate tonormal and balanced Na⁺, HCO₃ ⁻ and pH levels, and without formation ofCO₂ gas bubbles. A need also exists for ion-exchange materials andsorbent dialysis systems that can remove toxic metal and non-metal ionsfrom tap water in preparation of purified dialysate for dialysis.

SUMMARY OF THE PRESENT INVENTION

A feature of the present invention is to provide a sorbent cartridgethat avoids one or more of the above mentioned disadvantages.

Another feature of the present invention is to provide a sorbentcartridge that can regenerate spent dialysate and restore the levels ofNa⁺ and HCO₃ ⁻ to levels found in fresh dialysate.

Another feature of the present invention is to provide an improvedion-exchange material that releases a controlled amount of Na⁺ ions.

A further feature of the present invention is to provide a method ofregenerating spent dialysate without release of Na⁺ ions to thedialysate.

An additional feature of the present invention is to provide a dialysissystem that maintains a uniform level of Na⁺ in the dialysate.

Additional advantages of the present invention will be set forth in partin the description that follows, and in part will be apparent from thedescription, or may be learned by practice of the present invention. Thegoals and advantages of the present invention will be realized andattained by means of the elements particularly pointed out in theappended claims.

To achieve the above noted goals and in accordance with the purposes ofthe present invention, as embodied and broadly described herein, thepresent invention provides a sorbent cartridge comprising a combinationof acid zirconium phosphate (AZP) and alkaline hydrous zirconium oxide(NaHZO) in the sorbent cartridge. The combination of AZP and NaHZO canbe present as a homogeneous mixture wherein the AZP and the NaHZO areuniformly distributed as a layer in the sorbent cartridge. Thecombination of AZP and NaHZO can provide functional properties to thesorbent cartridge that may not be present in sorbent cartridgescomprising separate layers of ZrP and HZO.

The present invention also provides a sorbent cartridge comprising acombination of AZP and NaHZO in the cartridge, wherein the ratio of AZPto NaHZO can be varied, for example, to control the pH of regenerateddialysate, and/or to obtain the desired amount of sodium binding.

The present invention further provides a sorbent cartridge that can beused in an apparatus and/or system for conducting dialysis, for example,hemodialysis and/or peritoneal dialysis.

The present invention further provides a sorbent cartridge comprising acombination of AZP and NaHZO, and optionally further comprising ZrP. TheZrP can be titrated to a selected pH to control the functionalcharacteristics of the sorbent cartridge, for example, the desiredamount of sodium binding.

The present invention also provides a sorbent cartridge that isconfigured to restore the balance of Na⁺ and HCO₃ ⁻ in spent dialysateto levels found in fresh dialysate.

The present invention further provides a method to regenerate or purifyspent dialysate without releasing Na⁺, and/or generating CO₂ gasbubbles, in the dialysate.

The present invention also provides a method of preparing purifieddialysate for dialysis.

The present invention further provides a dialysis system that canregenerate spent dialysate while maintaining a uniform level of Na⁺ inthe dialysate.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary only and are notrestrictive of the present invention, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic diagram of sorbent cartridges according tovarious embodiments.

FIG. 1B is a schematic diagram of sorbent cartridges according tovarious embodiments.

FIG. 2 is a schematic diagram of a sorbent cartridge according tovarious embodiments.

FIG. 3 is a schematic diagram of a dialysis recirculation system.

FIG. 4 is a schematic diagram of a sorbent cartridge according tovarious embodiments.

FIG. 5 is a schematic diagram of a single pass dialysis system.

FIG. 6 is a schematic diagram of a sorbent cartridge according tovarious embodiments.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to materials useful for the removal ofwaste products and excess fluid that accumulates in dialysate fluids.These materials can be present in a container (e.g., a sorbentcartridge) capable of holding the materials useful for the removalprocess. The materials described in detail below, or the arrangement ofmaterials, can be used in a dialysis system or other similar type ofsystem that is useful for the removal of waste products and/or excessfluid that accumulates in dialysate fluids, for instance, as a result ofconducting hemodialysis or peritoneal dialysis. As described in moredetail below, the present invention is useful in purifying orregenerating dialysate used in hemodialysis and in peritoneal dialysis.Conventional dialysis solutions for peritoneal dialysis or hemodialysiscan be used and regenerated by the present invention and are known tothose skilled in the art.

The present invention, in part, relates to a sorbent cartridgecomprising a combination of acid zirconium phosphate (AZP) and alkalinehydrous zirconium oxide (NaHZO) in the sorbent cartridge. For purposesof the present invention, acid zirconium phosphate, or AZP, means the H⁺form of zirconium phosphate. AZP can have the following chemical andphysical properties:

Composition: (H⁺)_(x)(ZrO₂)(OH⁻)_(y)(PO₄)_(1.8-2.0).nH₂O

Ion-exchange formula: [ZrO₂(OH)_(y)(PO₄)₂]²⁻.H⁺ _(x)

Structural formula:

wherein x for H⁺ is 1.5 to 2.0, y for OH⁻ is 0.5 to 0, and n for H₂O andfor the structural formula is 1 to 4. x, y, and n can be any decimal inthese ranges and can optionally be above or below these ranges. The AZPcan have a hydrogen ion content of, for example, from about 2-10 mEqH⁺/g AZP, from about 4-8 mEq H⁺/g AZP, or from about 5-7 mEq H⁺/g AZP.The AZP can have a pH in water (1 g/100 ml) of, for example, about0.5-5, or about 1-3, and a pH in brine (1 g/100 ml) of, for example,about 0-5, or about 0.5-1.5.

For purposes of the present invention, alkaline hydrous zirconium oxide,or NaHZO, means the alkaline form of hydrous zirconium oxide (ZrO(OH)₂),in which the zirconium oxide is hydroxylated. NaHZO can have thefollowing chemical and physical properties:

Composition: Na⁺ _(x)ZrO₂(OH⁻)_(y).nH₂O

Ion-exchange formula: ZrO₂.OH⁻

Structural formula:

wherein x for Na⁺ is 1, y for OH⁻ is 2 to 4 and n for H₂O is 4 to 6, andx, y, and n can be any decimal in these ranges and can optionally beabove or below these ranges. The NaHZO can have a Na⁺ content Na:ZrO₂(molar ratio) in a range of, for example, from about 0.5:1.5, about 1:1,or about 1.5:0.5, and/or have a hydroxyl ion content in a range of, forexample, about 3-12 mEq OH⁻/10 g NaHZO, about 5-10 mEq OH⁻/10 g NaHZO,or about 6-9 mEq OH⁻/10 g NaHZO. The NaHZO can have a pH in water (1g/100 ml) of, for example, about 7-14, about 9-12, or about 10-11.

The present invention, in part, is based on the following mechanisms:(1) conversion of carbonic acid and CO₂ gas back to HCO₃ ⁻ by thealkaline NaHZO after NaHCO₃ is decomposed by AZP, and/or (2) switch ofthe ion-exchange mechanism from adsorbed Na⁺ of ZrP to lattice H⁺ ionsof AZP so that there is no release of Na⁺. For example:

It was determined that the cationic ion-exchange properties of the H⁺form of ZrP (i.e. AZP) when acting alone, for example, in a separatelayer in a sorbent cartridge, does not readily release H⁺ in exchangefor NH₄ ⁺, Ca²⁺, K⁺ Mg²⁺, Na⁺, and other cations that may be present inspent dialysate. It was further determined that when in the presence ofbase, for example OH⁻, HCO₃ ⁻, or CO₃ ²⁻, the base can serve to extractthe H⁺ ions out from AZP which are then replaced by the cation adsorbed.Accordingly, when blended with NaHZO, for example, as a homogeneousmixture, the ion-exchange properties of AZP can be affected. The abilityof AZP, for example, to release H⁺ in exchange for other cationsincreases. A combination of AZP and NaHZO can efficiently absorb cationsfrom spent dialysate. Without wishing to be bound to any theory, onepossible reason may be that the OH⁻ groups present in NaHZO, and theirinteraction with H⁺ in AZP, may be responsible for the alteredion-exchange properties.

The anionic ion-exchange properties of NaHZO, having adsorptioncapacities for PO₄ ²⁻, F⁻, SO₄ ²⁻ and other anions, can be altered whenacted upon by an acidic pH, for example, a pH less than 7. In thepresence of acid, the NaHZO can be alkaline in water, releasing OH⁻ ionsin exchange for adsorption of other anions. The release of OH⁻ ions canremove acid entities from water (CO₂ gas or H⁺ ions) and keep the pH inthe neutral range (e.g., pH of 7 to 7.4).

The combination of AZP and NaHZO can also precisely control HCO₃ ⁻ bycontrolling the pH in regenerated dialysate in the range of, forexample, pH 3-4, and removing most (e.g., to a negligible amount) or allof the carbonic acid and CO₂. As a result, a desired amount of HCO₃ ⁻can then be proportioned back in to the dialysate, for example, at about35 mEq/L. The Na⁺ level can also be maintained constant in the dialysatedue to the switch to the H⁺ ion-exchange mechanism of AZP.

The present invention relates, in part, to a combination of AZP andNaHZO in a sorbent cartridge. The AZP/NaHZO combination can preventvariation of Na⁺, HCO₃ ⁻ and pH in regenerated dialysate during dialysistreatment. The alkaline NaHZO can convert carbonic acid and CO₂ back toNaHCO₃ so that bicarbonate level and pH are unchanged. The ion-exchangeof NH₄ ⁺, and electrolyte cations K⁺, Ca²⁺, and Mg²⁺, can switch fromNa⁺ to AZP lattice H⁺ ions throughout the dialysis treatment. Thus, AZPcan control Na⁺ variation in dialysate by binding and removing Na⁺ ionsfrom dialysate, and by not releasing Na⁺ to the dialysate.

The present invention also relates, in part, to combinations of AZP andNaHZO wherein the ratio of AZP to NaHZO can be varied. By lowering theproportion of NaHZO, the combination of AZP and NaHZO can control the pHof regenerated dialysate, for example, in the pH range of about 3-4. Inthis pH range, the bicarbonate in regenerated dialysate can becompletely converted to carbonic acid and CO₂ gas. Subsequently, precisebicarbonate control can be accomplished by proportioning in NaHCO₃, forexample, at a level of about 35 mEq/L, and thus restoring the pH back toa desired level, for example, physiological level, or a pH of about7-7.4.

The combination of AZP and NaHZO can be present together in thecartridge as at least one layer. The sorbent cartridge can comprise atleast two layers and the cartridge can comprise at least one other layerof sorbent material. The combination of AZP and NaHZO can be present inthe sorbent cartridge as AZP particles and NaHZO particles having anaverage size, for example, of from about 25 microns to about 60 microns.The combination of AZP and NaHZO can be present as a homogeneousmixture, wherein the AZP and the NaHZO are uniformly distributed ormixed amongst each other, for instance, as one or more layers, in thesorbent cartridge.

A sorbent cartridge comprising a combination of AZP and NaHZO in thesorbent cartridge can regenerate spent dialysate preferably withoutreleasing Na⁺ ions. The combination of AZP and NaHZO can also serve as auremic toxin adsorbent to remove urea (NH₄ ⁺ after urea hydrolysis byurease) and phosphate from spent dialysate.

The AZP can be prepared by a reaction between aqueous solutions of azirconium salt and phosphoric acid. The reaction forms a gelatinousprecipitate that is filtered and washed until excessive phosphoric acidis removed, and then dried in an oven, such as to a moisture level offrom about 12 to 18 weight percent Loss on Drying (LOD). Other LODs arepossible. The final product after drying can be a fine powder orgranules, such as with an irregular form. The AZP can comprise, forexample, particles having an average particle size of about 5-100microns, about 10-80 microns, about 25-60 microns, or about 25-45microns. The average grain size is not limited to these ranges and canbe sizes above or below these ranges.

The AZP can be prepared, for example, by following the methods disclosedin U.S. Pat. No. 6,818,196, which is incorporated in its entirety byreference herein. Briefly, AZP can be prepared by heating zirconiumoxychloride (ZOC) with soda ash to form sodium zirconium carbonate, andtreating the sodium zirconium carbonate with caustic soda to formalkaline hydrous zirconium oxide. An aqueous slurry of the alkalinehydrous zirconium oxide can then be heated while adding phosphoric acidand an acid zirconium phosphate recovered. An aqueous slurry of the AZPcan also be titrated with a basic agent, such as caustic soda, until adesired pH is reached, for example, a pH of from about 5 to about 7.

Alternatively, the AZP can be prepared by heating an aqueous mixture ofbasic zirconium sulfate (BZS) and phosphoric acid at a sufficienttemperature (e.g., 180° F.-190° F.) and for a sufficient time (e.g., 1-2hr) to form acid zirconium phosphate precipitate. Then the solution canbe cooled and the acid zirconium phosphate can be filtered and washed toreduce unreacted leachable phosphate levels. The AZP particles can befurther dried, for example, at about 120° F.-170° F. The AZP particlescan have a BET surface area of less than 2 m²/g. By way of example, theAZP can be prepared as described in Example 1.

The AZP can be prepared, for example, by following the methods disclosedin U.S. Patent Application Publication 2006/0140840, which isincorporated in its entirety by reference herein in combination with theteachings provided herein. Briefly, AZP can be prepared by preparing asolution of zirconium oxychloride (ZOC) and an organic chemical additivein water, and then titrating with concentrated hydrochloric acid (HCl)to fully dissolve the precipitate. This ZOC solution is then added to asolution of phosphoric acid to produce a slurry of AZP precipitate. Theprecipitate is then filtered and washed. The AZP particles can have aBET surface area greater than 10 m²/g. By way of example, AZP can beprepared as described in Example 2.

Alkaline hydrous zirconium oxide can be prepared by the reaction of azirconium salt, for example, BZS, or its solution in water with analkali metal (or alkali metal compound) at ambient temperature, to forma NaHZO precipitate. The NaHZO particles can be filtered and washeduntil the anions of the zirconium salt are completely removed, and thenpreferably air dried, or dried in an oven at mild temperature (e.g., 60°F. to less than 90° F.) to a moisture level, for instance, of from about25-30 weight percent LOD or lower, to form a free-flowing powder. OtherLODs can be achieved, although higher temperature (e.g. 90° F.-120° F.)and/or long drying time (e.g. 24-48 hrs) to achieve a lower moisturelevel (i.e., <20 weight percent LOD) can convert the zirconium-hydroxidebond to a zirconium-oxide bond and reduce the adsorption capacity aswell as alkalinity of the anion-exchange material. The dryingtemperatures refer to the nominal temperature in the oven or dryer. TheNaHZO can comprise particles having an average grain size of about10-100 microns, about 20-80 microns, about 25-60 microns, or about 25-40microns. The average grain size is not limited to these ranges and canbe sizes above or below these ranges. The NaHZO can have a BET surfacearea of less than 2 m²/g (e.g., 0.1 to 1.9 m²/g, 0.5 to 1.5 m²/g, 0.8 to1.2 m²/g). By way of example, the NaHZO can be prepared as described inExample 3.

The NaHZO can be prepared, for example, by following the methodsdisclosed in U.S. Patent Application Publication 2006/0140840, which isincorporated in its entirety by reference herein, in combination withthe teachings provided herein. Briefly, this method of preparing NaHZOinvolves adding an aqueous solution of ZOC, titrated with concentratedHCl, to an aqueous solution of caustic soda. The HCl addition canprevent excessive gelation during the precipitation process as well asto promote particle growth. The NaHZO particles can have a BET surfacearea of greater than 10 m²/g. By way of example, the NaHZO can beprepared as described in Example 4.

The AZP and NaHZO of the present invention can be present as a layer (orlayers) in sorbent cartridges such as those described in U.S. Pat. No.7,033,498 B2, and U.S. Pat. No. 6,878,283 B2, in Sorb Technology's REDYcartridge, and in Renal Solution's Allient cartridge (e.g., see “SorbentDialysis Primer,” COBE Renal Care, Inc. Sep. 4, 1993 edition), allincorporated in their entirety by reference herein. For example, variousfilter media sections within a tubular housing or cartridge can be usedwith the AZP and NaHZO of the present invention. The housing orcartridge can include a sorbent material like a granular activatedcarbon section, an immobilized enzyme section, a powdered alumina(Al₂O₃) section, and/or a zirconium phosphate (ZrP) section, or anycombinations thereof. The ZrP can be prepared, for example, as describedin U.S. Published Patent Application No. 2006/0140840, incorporated inits entirety by reference herein. The amounts for each component can beas stated in the above patents and exemplary amounts are provided in thefigures. Depending on the application, the AZP/NaHZO layer can be usedin an amount, for example, of from about 200-1700 g per dialysiscartridge, such as from about 500-600 g per cartridge used inhemodialysis, or from about 200-1200 g per cartridge used in peritonealdialysis.

The AZP and NaHZO can be present in any desired weight ratio. The weightratio of NaHZO:AZP can range, for example, from about 0.1:0.9 to about0.9:0.1, from about 0.2:0.8 to about 0.8:0.2, from about 0.22:0.78 toabout 0.33:0.67, from about 0.5:0.5 to about 0.6:0.4, or about 0.4:0.6.The various weight ratios of AZP and NaHZO can provide a mixture havingany desired pH. A mixture of AZP and NaHZO can have a pH, for example,from about 3 to about 9, from about 3 to about 7, from about 3.5 toabout 4, from about 4 to about 5.5, or from about 5.5 to about 6.

The sorbent cartridge can further comprise ZrP. The ZrP can be presentas a separate layer(s) in the sorbent cartridge. The ZrP can be titratedto have any desired pH, for example, a pH from about 3 to about 9, fromabout 3 to about 7, from about 3.5 to about 4, from about 4 to about5.5, or from about 5.5 to about 6. Sorbent cartridges comprising acombination of AZP and NaHZO in various amounts and ratios, and invarious pH levels, and/or providing ZrP in a variety of pH levels, canprovide desired effects on the performance of dialysate regeneration, asfurther detailed below.

The sorbent cartridge can further comprise activated carbon, enzyme,alumina, or combinations thereof. The activated carbon, enzyme, and/oralumina can each be present as separate layers in the sorbent cartridge.The enzyme can be, for example, urease, and the enzyme can beimmobilized.

The sorbent cartridge can be a cartridge that contains one or morelayers or zones of the AZP particles and NaHZO particles, wherein thesorbent cartridge has a plurality of filter media sections (or layers)including an arrangement, starting from a first end (inlet) and endingat a second end (outlet), an activated carbon section, an immobilizedenzyme section, a powdered alumina section, and an AZP/NaHZO section(for example, as a composite). The arrangement can optionally furtherinclude a ZrP section located before and/or after the AZP/NaHZO section,and/or can optionally include a sodium zirconium carbonate layer beforeand/or after the AZP/NaHZO section.

The composition of the present invention can be used in any applicationin sorbent cartridges as a layer with one or more layers described forinstance in U.S. Published Patent Application No. 2002-0112609 and U.S.Pat. No. 6,878,283 B2, and in Sorb's REDY cartridge (e.g., see “SorbentDialysis Primer,” COBE Renal Care, Inc. Sep. 4, 1993 edition, and “RxGuide to Custom Dialysis,” COBE Renal Care, Inc. Revision E, September,1993), all incorporated in their entirety by reference herein. Forexample purposes only, various filter media sections within a tubularhousing or cartridge can be used with the composition of the presentinvention. The composition of the present invention can be used incombination with or in place of any zirconium phosphate layer. Thecomposition of the present invention can be used as a layer in thesorbent cartridge described in U.S. Pat. Nos. 6,627,164; 6,878,283;7,033,498; or published Application No. 2006/0140840, incorporated byreference herein.

For dialysis, a filter medium adapted to remove chlorine from tap wateris preferred unless purified water is used as a base for the dialysate.The filter medium can be activated carbon. Activated carbon can also beused as a filter medium to bind heavy metals, oxidants, and chloramines.An immobilized enzyme such as urease can be used in a filter medium toconvert urea to ammonium carbonate by enzymatic conversion. Urease canbe immobilized by adsorption, covalent bonding, intermolecularcross-linking, entrapment within cross-linked polymers,microencapsulation, and containment within a semipermeable membranedevice. Alumina (Al₂O₃), activated carbon, anion-exchange resins, anddiatomaceous earth can be used as adsorbents. The use of activatedcarbon to remove chlorine, if used, can precede the immobilized enzymemedium because chlorine can deactivate the enzyme. Cation exchangematerials can be used to bind ammonium, calcium, magnesium, potassium,and other cations as well as toxic trace metals in tap water. Suchcation exchange materials can include AZP and ZrP. Anion exchangematerials can bind phosphate, fluoride, and other heavy metals. Suchanion exchange materials can include NaHZO.

Sorbent cartridges for regenerative dialysis can be configured as shown,for example, in FIG. 1A and in FIG. 1B. In FIG. 1A, a sorbent cartridge(Model I) can comprise a carbon layer, an immobilized urease layer, andan AZP and NaHZO combination (NaHZO/AZP layer) in the sorbent cartridge.In the top example of FIG. 1A, the AZP and NaHZO can be present in thesorbent cartridge in an amount and proportion such that the weight ratioof NaHZO:AZP is in a range of from about 0.5:0.5 to about 0.6:0.4. Insuch a configuration, the amount and ratio of AZP and NaHZO can beadjusted to obtain a uniform concentration of Na⁺, HCO₃ ⁻, and a pH ofabout 5.5-6.0. In the bottom example of FIG. 1A, the AZP and NaHZO canbe present in the sorbent cartridge in an amount and proportion suchthat the weight ratio of NaHZO:AZP is in a range of from about 0.22:0.78to about 0.33:0.67. In such a configuration, the amount and proportionof AZP and NaHZO can be adjusted to obtain a uniform concentration ofNa⁺, a pH of 3-4, and complete removal of HCO₃ ⁻.

As shown by the examples in FIG. 1B, a sorbent cartridge (Model II) cancomprise a carbon layer, an immobilized urease layer, an AZP and NaHZOcombination layer, and a ZrP layer in the sorbent cartridge. The ZrPlayer can be titrated to a desired pH. The amount and proportion of AZPand NaHZO, and the amount and pH of titrated ZrP, can be adjusted toobtain a uniform concentration of Na⁺ and HCO₃ ⁻, and a desired uniformpH level. In the top example of FIG. 1B, the AZP and NaHZO can bepresent in the sorbent cartridge in an amount and proportion such thatthe weight ratio of NaHZO:AZP is in a range of from about 0.5:0.5 toabout 0.6:0.4, and the ZrP can be titrated in a range of from about pH5.5-6.0. In the bottom example of FIG. 1B, the AZP and NaHZO can bepresent in the sorbent cartridge in an amount and proportion such thatthe weight ratio of NaHZO:AZP is about 0.4:0.6, and the ZrP can betitrated in a range of from about pH 3.5-4.0. In such a configuration, auniform concentration of Na⁺, a pH of 3.5-4, and complete removal ofHCO₃ ⁻, can be obtained.

A sorbent cartridge comprising a combination of AZP and NaHZO in thesorbent cartridge can be capable of restoring the balance of Na⁺ andHCO₃ ⁻ in spent dialysate to the levels found in fresh dialysate. Thesorbent cartridge can comprise a composite of AZP and NaHZO as detailedabove. A sorbent cartridge comprising an AZP/NaHZO composite caneffectively remove NH₄ ⁺ and other cations from spent dialysate withoutreleasing Na⁺ ions, and without producing CO₂ gas bubbles.

A sorbent cartridge comprising a combination of AZP and NaHZO asdetailed above can be utilized to regenerate or purify spent dialysate.A method to regenerate or purify spent dialysate can comprise passingthe spent dialysate through a sorbent cartridge comprising a combinationof AZP and NaHZO, as detailed above. In some methods, the sorbentcartridge can further comprise ZrP.

In some methods, the spent dialysate can be regenerated to essentiallyrestore the original balance of Na⁺ and HCO₃ ⁻ contents found in freshdialysate. The spent dialysate can be regenerated to comprise a Na⁺content of, for example, from about 90 mEq/L to about 180 mEq/L, fromabout 100 mEq/L to about 160 mEq/L, or from about 110 mEq/L to about 150mEq/L. The spent dialysate can be regenerated to comprise a HCO₃ ⁻content of, for example, from about 20 mEq/L to about 40 mEq/L, fromabout 22 mEq/L to about 38 mEq/L, or from about 25 mEq/L to about 35mEq/L. In some methods, the spent dialysate can be regenerated toessentially restore the original pH of fresh dialysate. The dialysatecan be regenerated to a pH, for example, of from about 6.5 to about 8,or from about 6.8 to about 7.4. The dialysate can be regenerated orpurified without release of Na⁺ to the dialysate.

The dialysate can be regenerated with little or no generation of CO₂ gasbubbles. Spent dialysate can be passed through a sorbent cartridgecomprising a combination of AZP and NaHZO as detailed above. The NaHCO₃present in the spent dialysate can be decomposed by the AZP to formcarbonic acid and CO₂. Then, at acidic pH, (e.g. pH <6.5) the carbonicacid and the CO₂ can be converted by the NaHZO to form NaHCO₃.

A sorbent cartridge comprising a combination of AZP and NaHZO asdetailed above can be utilized to prepare purified dialysate fordialysis. The dialysate can comprise tap water. The sorbent cartridgecan act as a dialysate purification system. Dialysate levels of bacteriaand endotoxin can be maintained, for example, at <1 CFU/ml bacteria and<0.3 EU/ml endotoxin.

An apparatus for conducting dialysis can comprise a sorbent cartridgecomprising a combination of AZP and NaHZO as detailed above, and adialyzer in fluid communication with the sorbent cartridge, whereinspent dialysate passes from the dialyzer to and through the sorbentcartridge. The spent dialysate can be spent hemodialysate, spentperitoneal dialysate, or combinations thereof. The dialyzer can be influid communication with the blood of a patient.

A dialysis system can comprise a sorbent cartridge comprising acombination of AZP and NaHZO as detailed above, and a source of spentdialysate, wherein the source of the spent dialysate is in fluidcommunication with the sorbent cartridge and the spent dialysate passesto and through the sorbent cartridge. The spent dialysate can passthrough the sorbent cartridge at a rate of from about 10 ml/min to about1000 ml/min, from about 100 ml/min to about 550 ml/min, or from about150 ml/min to about 400 ml/min. The dialysis system can regenerate thespent dialysate, and can regenerate the spent dialysate to a pH levelapproximately equal to that of fresh dialysate. The system can alsoregenerate the spent dialysate without the formation of CO₂ gas bubbles.The system can furthermore maintain a uniform level of Na⁺ while thespent dialysate is being regenerated.

The following examples are given to illustrate the nature of theinvention. It should be understood, however, that the present inventionis not limited to the specific conditions or details set forth in theseexamples.

EXAMPLES Example 1

One (1) kg of BZS was added to deionized water in a reactor to form aslurry with moderate agitation speed. Then, about 770 ml Technical Gradephosphoric acid (76%) diluted with equal volume of water was pumped intothe slurry. With slow agitation, the slurry was heated at moderate ormaximum rate to 180-185° F., and then heated to maintain thattemperature for one hour after the temperature was reached. The slurrywas then cooled to room temperature. The product was filtered and washedin a Buchnell funnel with deionized water. The filter cake was thendried in a tray dryer at 180° F. until the moisture level was 12-18weight percent LOD. The particle size was in a range of from 25-60microns.

Example 2

Solution A was prepared as follows: 20 g ZOC crystals was dissolved in15 ml deionized water and 15 ml isopropanol was added to the solution.Then, with agitation by magnetic stirrer or plastic impeller, about 100drops of concentrated HCl was added to the solution with continuedagitation until all precipitate was redissolved to form a clearsolution.

Solution B was prepared as follows: 30 g Technical Grade phosphoric acid(76%) was diluted in 60 ml water in a 500 ml beaker. With a magneticstirrer, the diluted acid was heated to a boiling temperature.

Reaction process steps:

-   -   Step 1: Solution A was pumped into Solution B at boiling        temperature at about 10 ml/min flow rate, with moderate        agitation speed using magnetic stirrer or plastic impeller.    -   Step 2: After addition was complete to produce a slurry of        precipitate, the slurry was heated for one hour to evaporate off        the alcohol completely and improve crystal structure of the AZP        precipitate.    -   Step 3: After heating for one hour, the slurry was allowed to        cool. The precipitate was then filtered and washed with        deionized water to remove excessive unreacted phosphoric acid.    -   Step 4: The washed product was dried in an oven at 180° F. until        the moisture level was 5-20 weight percent LOD to form a        free-flowing powder. The particle size was in a range of from        25-45 microns.

Example 3

500 g BZS was added to 430 ml deionized water in a 1-liter beaker toform a slurry with mild agitation. Then 40 ml 50% NaOH was added to theslurry to elevate the pH to about 6.5. The material was filtered andwashed 3 times with 500 ml deionized water in a Buchnell funnel. Withmild agitation, the filter cake was transferred to an alkali solutionwith higher alkaline strength made up by mixing 140 ml 50% NaOH with 125ml deionized water. The pH of the slurry was checked and an additionalamount of NaOH was added if necessary to obtain pH above 12.5. Theslurry was then agitated for 30 minutes. The product was filtered in aBuchnell funnel fitted with glass fiber filter then washed withdeionized water until the leachable sulfate could not be detected in thefiltrate by applying the BaCl₂ reagent test. The filter cake wastransferred to a tray dryer at approximately 110° F. and the materialdried to a moisture level of about 25 to 30 weight percent LOD to form afree-flowing powder. The particle size was in a range of from 25 to 60microns.

Example 4

Solution A was prepared as follows: 20 g ZOC crystals was dissolved in50 ml deionized water at room temperature. Approximately 100 drops ofconcentrated HCl was added to the solution with mild agitation using amagnetic stir bar.

Solution B was prepared as follows: 100 ml Technical Grade caustic soda(50% NaOH) was diluted with 300 ml deionized water in a 500 ml beaker atroom temperature to obtain approximately a 12.5% NaOH solution (about3N).

Reaction process steps:

-   -   Step 1: Solution A was pumped into Solution B at room        temperature at the flow rate of about 10 ml/min with vigorous        agitation speed using a magnetic stirrer or plastic impeller.        The pH was monitored during the precipitation process to ensure        the pH was still above 12.0 at the end.    -   Step 2: After addition was complete to produce a slurry of        precipitate, the vigorous agitation was continued for 30 minutes        to allow the particles to become hardened.    -   Step 3: The filter cake was transferred to a tray dryer at about        110° F. and the material dried to the moisture level of        approximately 25 to 35 weight percent LOD to form a free-flowing        powder. The particle size was in a range of about 25-40 microns.

Example 5

Cartridge effluent with Na⁺, HCO₃ ⁻, and pH restored to normal range.

Step 1: A column was prepared with the configuration as shown in FIG. 2(2-inch diameter polycarbonate column).

Step 2: A 6 L bath was prepared at approximately 36° C. to simulatespent dialysate (i.e., after passing through dialyzer) with acomposition shown as follows:

Na⁺ 135 mEq/L  Mg²⁺ 1 mEq/L Ca²⁺ 3 mEq/L K⁺ 2 mEq/L HCO₃ ⁻ 30 mEq/L  pH7.0-7.4 Cl⁻ 105 mEq/L  PO₄—P 5 mg/dL BUN 20 mg/dL  Creatinine 10 mg/dL 

Step 3: A recirculation system was set up as shown in FIG. 3

The spent dialysate was re-circulated through the column at a flow rateof about 80 ml/min. Urea was re-infused into the 6 L bath to maintainthe urea-N concentration at about 20 mg/dL urea-N during there-circulation. Ten ml samples of cartridge effluent were collected (atLocation {circle around (1)} and 10 ml samples of the 6 L bath werecollected (at Location {circle around (2)} according to the followingschedule: Initial, 5 min, 10 min, 15 min, 30 min, 60 min, 120 min.

The time variation of dialysate composition in the cartridge effluentand the 6 L spent dialysate bath are shown in TABLE 1 and TABLE 2.

TABLE 1 Time variation of dialysate composition in cartridge effluent atLocation {circle around (1)} Cartridge effluent at Location Na HCO₃ ⁻PO₄—P BUN NH₄ ⁺—N Creatinine Ca²⁺Mg²⁺K⁺ {circle around (1)} pH mEq/LmEq/L mg/dL mg/dL mg/dL mg/dL mEq/L Initial 7.12 129 31 0.13 0 0.03 0.2<0.2  5 min 6.50 126 31 0.14 0 0.03 0.2 <0.2 10 min 6.20 130 29 0.20 00.03 0.2 <0.2 15 min 6.50 135 32 0.13 0 0.03 0.2 <0.2 30 min 6.56 136 300.20 0 0.03 0.2 <0.2 60 min 6.78 136 30 0.36 0 0.05 0.2 <0.2 120 min 7.46 141 36 0.10 0.2 2.22 0.2 <0.2

TABLE 2 Time variation of dialysate composition in the 6 L spentdialysate bath at Location {circle around (2)} BUN 6 L spent mg/dLdialysate at Na HCO₃− PO₄—P (with re- NH₄ ⁺—N Creatinine Ca²⁺ Mg²⁺ K⁺Location {circle around (2)} pH mEq/L mEq/L mg/dL infusion) mg/dL mg/dLmEq/L mEq/L mEq/L Initial 7.30 135 30 5 20 — 10 3 2 1  5 min 7.29 129 320.30 19.4 — 2 — — — 10 min 6.76 132 33 0.20 18.3 — 0.2 — — — 15 min 6.61133 30 0.15 16.5 — 0.2 — — — 30 min 6.67 130 36 0.26 23.7 — 0.2 — — — 60min 6.72 130 34 0.13 26.8 — 0.2 — — — 120 min  7.13 140 36 0.15 24.7 —0.2 — — —

Example 6

The test in Example 5 was repeated by using 2 L spent dialysate bathinstead. The time variation of the dialysate bath composition atLocation {circle around (2)} is shown in TABLE 3.

TABLE 3 Time variation of dialysate composition in the 2 L spentdialysate bath at Location {circle around (2)} BUN 2 L spent mg/dLdialysate at Na HCO₃ ⁻ PO₄—P (with re- NH₄ ⁺—N Creatinine Ca²⁺ Mg²⁺ K⁺Location {circle around (2)} pH mEq/L mEq/L mg/dL infusion) mg/dL mg/dLmEq/L mEq/L mEq/L Initial 7.16 134 31 5 21 — 0.2 3 2 1  5 min 7.23 12933 0.23 17 — 0.2 — — — 10 min 7.10 131 32 0.14 16 — 0.2 — — — 15 min6.71 129 28 0.11 18 — 0.2 — — — 30 min 6.80 130 29 0.08 21 — 0.2 — — —60 min 6.68 131 27 0.07 22 — 0.2 — — — 120 min  7.19 147 35 0.12 24 —0.2 — — —

Example 7

The test in Example 5 was repeated by using 1 L spent dialysate bathinstead. The time variation of the dialysate bath composition atLocation {circle around (2)} is shown in TABLE 4.

TABLE 4 Time variation of dialysate composition in the 1 L spentdialysate bath at Location {circle around (2)} BUN 1 L spent mg/dLdialysate at Na HCO₃ ⁻ PO₄—P (with re- NH₄ ⁺ Creatinine Ca²⁺ Mg²⁺ K⁺Location {circle around (2)} pH mEq/L mEq/L mg/dL infusion) mg/dL mg/dLmEq/L mEq/L mEq/L Initial 7.02 133 31 5 18.7 — 0.2 3 2 1  5 min 7.02 12828 0.16 19.7 — 0.2 — — — 10 min 6.61 126 27 0.21 19.1 — 0.2 — — — 15 min6.80 125 24 0.08 23.7 — 0.2 — — — 30 min 6.60 126 28 0.09 21.8 — 0.2 — —— 60 min 6.60 128 29 0.10 25.4 — 0.2 — — — 120 min  7.20 135 34 0.0726.3 — 0.2 — — —

Example 8

Cartridge effluent with pH control at 2.4-3.0 by cartridge leading tocomplete HCO₃ ⁻ removal by CO₂ degassing, followed by bicarbonateinfusion to control HCO₃ ⁻ level at 30-35 mEq/L.

Step 1: A column was prepared with the configuration as shown in FIG. 4.

Step 2: A 144 L bath at approximately 36° C. was prepared to simulatespent dialysate for a 255 minute treatment time (i.e., after passingthrough dialyzer) with the composition shown below. This compositionrepresented the actual fluid composition at the inlet of the cartridgethroughout the actual treatment except for the varying BUN level duringthe treatment.

Na⁺ 140 mEq/L  HCO₃ ⁻ 35 mEq/L  Cl⁻ 105 mEq/L  pH 7.0-7.4 Mg²⁺ 1 mEq/LCa²⁺ 3 mEq/L K⁺ 2 mEq/L PO₄—P 2 mg/dL BUN 25 mg/dL  Creatinine 20 mg/dL 

Step 3: A single pass system was set up as shown in FIG. 5.

Step 4: The spent dialysate was pumped through the cartridge in thesingle pass mode at the flow rate of 550 ml/min. NaHCO₃ was re-infusedto the bicarbonate-free dialysate after CO₂ degassing to restore andmaintain bicarbonate level at 35 mEq/L. The Na⁺ was also controlled atapproximately 140 mEq/L by the additional Na⁺ from NaHCO₃ (as well asincrease the fluid volume from the infusate) before the regenerateddialysate was returned to the dialyser. Twenty (20) ml samples werecollected from the bath, at Location {circle around (1)} before NaHCO₃re-infusion, and at Location {circle around (2)} after NaHCO₃re-infusion according to the following schedule: Location {circle around(1)} (before NaHCO₃ re-infusion)—initial, 10 min, 20 min, 30 min, 45min, 60 min, 90 min, 120 min, 150 min, 180 min, 195 min, 210 min, 225min, 240 min, 255 min; Location {circle around (2)} (after NaHCO₃re-infusion)—30 min, 60 min, 120 min, 180 min.

The time variation of dialysate composition in the cartridge effluentbefore NaHCO₃ re-infusion at Location{circle around (1)}, and after atLocation{circle around (2)}, are shown in TABLE 5 and TABLE 6.

TABLE 5 Dialysate composition data in the cartridge effluent after CO₂degassing but before NaHCO₃ re-infusion at Location {circle around (1)}Time (min) 0 10 20 30 45 60 90 120 NH₄ ⁺ 0 0 0 0 0 0 0 0 pH 6.03 2.402.40 2.41 2.37 2.44 2.58 2.58 Na⁺ 114 116 115 114 114 114 114 114(mEq/L) HCO₃ ⁻ 0 0 0 0 0 0 0 0 (mEq/L) Cl⁻ 105 106 105 106 105 106 105106 (mEq/L) Ca²⁺ <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 (mEq/L) K⁺ <0.2<0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 (mEq/L) Mg²⁺ <0.1 <0.1 <0.1 <0.1 <0.1<0.1 <0.1 <0.1 (mEq/L) BUN 0 0 0 0 0 0 0 0 (mg/dL) Creatinine <0.2 <0.2<0.2 <0.2 <0.2 <0.2 <0.2 <0.2 (mg/dL) PO₄ ⁻P 0.06 0.08 0.04 0.01 0.010.01 0.01 0.01 (mg/dL) Time (min) 150 180 195 210 225 240 255 NH₄ ⁺ 0 00 0.1 0.1 0.1 0.3 pH 2.47 2.48 2.46 2.45 2.56 3.21 5.46 Na⁺ 113 114 114114 115 112 120 (mEq/L) HCO₃ ⁻ 0 0 0 0 0 0 2.3 (mEq/L) Cl⁻ 106 105 105105 105 105 105 (mEq/L) Ca²⁺ <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 (mEq/L)K⁺ <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 (mEq/L) Mg²⁺ <0.1 <0.1 <0.1 <0.1<0.1 <0.1 <0.1 (mEq/L) BUN 0 0 0 0 0 0 0 (mg/dL) Creatinine <0.2 <0.2<0.2 <0.2 <0.2 <0.2 <0.2 (mg/dL) PO₄ ⁻P 0.01 0.03 0.02 0.01 0.2 0.6 1.37(mg/dL)

TABLE 6 Na⁺ and HCO₃ ⁻ levels in the cartridge effluent after NaHCO₃re-infusion at Location {circle around (2)} Time (min) 30 60 120 180 pH7.08 7.02 7.10 7.19 Na⁺ (mEq/L) 142 142 142 142 (after dilution byre-infusion) HCO₃ ⁻ (mEq/L) 33 33.5 34 34.5

Example 9

Test in Example 8 was repeated but by the cartridge with a configurationas shown in FIG. 6. The time variation of regenerated dialysatecomposition before and after NaHCO₃ infusion is shown in TABLE 7 andTABLE 8.

TABLE 7 Dialysate composition data in the cartridge effluent after CO₂degassing but before NaHCO₃ re-infusion at Location {circle around (1)}Time (min) 0 10 20 30 45 60 90 120 150 NH₄ ⁺—N 0 0 0 0 0 0 0 0 1.05 pH6.76 2.70 2.53 2.50 2.51 2.53 2.50 2.51 2.50 Na⁺ 115 114 115 114 115 115114 114 115 (mEq/L) HCO₃ ⁻ 0 0 0 0 0 0 0 0 0 (mEq/L) Cl⁻ 105 106 104 105104 106 105 105 104 (mEq/L) Ca²⁺ <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2<0.2 (mEq/L) K⁺ <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 (mEq/L)Mg²⁺ <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 (mEq/L) BUN 0 0 0 0 00 0 0 0.1 (mg/dL) Creatinine <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2<0.2 (mg/dL) PO₄ ⁻P 0.04 0.03 0.01 0.05 0.07 0.08 0.06 0.07 0.05 (mg/dL)

TABLE 8 Na⁺ and HCO₃ ⁻ levels in the cartridge effluent after NaHCO₃re-infusion at Location {circle around (2)} Time (min) 30 60 120 180 pH7.01 7.04 7.15 7.20 Na⁺ (mEq/L) (after dilution by re-infusion) 142 143142 142 HCO₃ ⁻ (mEq/L) 31 32 31 33

Applicants specifically incorporate the entire contents of all citedreferences in this disclosure. Further, when an amount, concentration,or other value or parameter is given as either a range, preferred range,or a list of upper preferable values and lower preferable values, thisis to be understood as specifically disclosing all ranges formed fromany pair of any upper range limit or preferred value and any lower rangelimit or preferred value, regardless of whether ranges are separatelydisclosed. Where a range of numerical values is recited herein, unlessotherwise stated, the range is intended to include the endpointsthereof, and all integers and fractions within the range. It is notintended that the scope of the invention be limited to the specificvalues recited when defining a range.

Other embodiments of the present invention will be apparent to thoseskill in the art from consideration of the present specification andpractice of the present invention disclosed herein. It is intended thatthe present specification and examples be considered as exemplary onlywith a true scope and spirit of the invention being indicated by thefollowing claims and equivalents thereof.

What is claimed is:
 1. A sorbent cartridge comprising a layer of amixture of acid zirconium phosphate (AZP) and alkaline hydrous zirconiumoxide (NaHZO) in the sorbent cartridge, and wherein said acid zirconiumphosphate is the only form of zirconium phosphate present in said layer.2. The sorbent cartridge of claim 1, wherein the cartridge comprises atleast two layers, wherein at least one of the layers comprises thecombination of AZP and NaHZO.
 3. The sorbent cartridge of claim 1,wherein the AZP and the NaHZO comprise particles having an average grainsize of from about 25 microns to about 60 microns.
 4. The sorbentcartridge of claim 1, wherein the combination has a pH of from about 3to about
 7. 5. The sorbent cartridge of claim 1, wherein the combinationhas a pH of from about 3.5 to about
 4. 6. The sorbent cartridge of claim1, wherein the combination has a pH of from about 5.5 to about
 6. 7. Thesorbent cartridge of claim 1, wherein the AZP and NaHZO are each presentin the combination in an amount to produce an NaHZO:AZP weight ratio offrom about 0.2:0.8 to about 0.8:0.2.
 8. The sorbent cartridge of claim7, wherein the NaHZO:AZP weight ratio is from about 0.5:0.5 to about0.6:0.4.
 9. The sorbent cartridge of claim 7, wherein the NaHZO:AZPweight ratio is about 0.4:0.6.
 10. The sorbent cartridge of claim 7,wherein the NaHZO:AZP weight ratio is from about 0.22:0.78 to about0.33:0.67.
 11. The sorbent cartridge of claim 1, further comprisingzirconium phosphate (ZrP) as an additional layer in the sorbentcartridge.
 12. The sorbent cartridge of claim 11, wherein the ZrP has apH of from about 3 to about
 7. 13. The sorbent cartridge of claim 11,wherein the ZrP has a pH of from about 3.5 to about
 4. 14. The sorbentcartridge of claim 11, wherein the ZrP has a pH of from about 5.5 toabout
 6. 15. The sorbent cartridge of claim 1, further comprisingactivated carbon, immobilized urease, or combinations thereof.
 16. Thesorbent cartridge of claim 15, wherein the activated carbon and theimmobilized urease are each present as a layer in the sorbent cartridge.17. The sorbent cartridge of claim 1, wherein the sorbent cartridge isconfigured to restore the balance of Na⁻ and HCO₃ ⁻ in spent dialysateto levels found in fresh dialysate.
 18. A method to regenerate or purifyspent dialysate comprising passing the spent dialysate through thesorbent cartridge of claim
 1. 19. A method to regenerate or purify spentdialysate comprising passing the spent dialysate through the sorbentcartridge of claim
 11. 20. The method of claim 18, wherein the methodcomprises restoring the spent dialysate to original balance of Na⁺ andHCO₃ ⁻ contents found in fresh dialysate.
 21. The method of claim 18,wherein the method comprises restoring the spent dialysate to originalpH of fresh dialysate.
 22. The method of claim 18, wherein theregenerated dialysate has a pH from about 6.8to about 7.4.
 23. Themethod of claim 18, wherein the regenerated dialysate has a Na⁻ contentfrom about 110 mEq/L to about 150 mEq/L.
 24. The method of claim 18,wherein the regenerated dialysate has a HCO₃ ⁻ content from about 25mEq/L to about 35 mEq/L.
 25. The method of claim 18, wherein thedialysate is regenerated without generating CO₂ gas bubbles.
 26. Themethod of claim 18, wherein the dialysate is regenerated withoutreleasing Na⁺ to the dialysate.
 27. The method of claim 18, whereinNaHCO₃ present in spent dialysate is converted by the AZP to formcarbonic acid and CO₂, and the carbonic acid and the CO₂, are convertedby the NaHZO to form NaHCO₃.
 28. A method of preparing purified freshdialysate for dialysis comprising passing the dialysate through thesorbent cartridge of claim
 1. 29. The method of claim 28, wherein thedialysate comprises tap water.